title: Association of polymorphisms in FADS gene with age-related changes in serum phospholipid polyunsaturated fatty acids and oxidative stress markers in middle-aged nonobese men.
abstract: BACKGROUND
  To investigate the association of FADS gene polymorphisms with age-related changes in polyunsaturated fatty acids (PUFAs) in serum phospholipids and oxidative stress markers.
  
  
  METHODS
  We genotyped 122 nonobese men aged 35-59 years without any known diseases at baseline for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778), and followed them for 3 years.
  
  
  RESULTS
  Among the four single-nucleotide polymorphisms, the minor variants of rs174537 and rs2727270 were significantly associated with lower concentrations of long-chain PUFAs. However, rs174537G > T showed stronger association. At baseline, men with the rs174537T allele had lower arachidonic acid (AA) and AA/linoleic acid (LA), and higher interleukin (IL)-6 levels than rs174537GG counterparts. After 3 years, rs174537GG men had significantly increased AA (P = 0.022), AA/dihomo-γ-linolenic acid (DGLA) (P = 0.007), docosapentaenoic acid (DPA), low-density lipoprotein (LDL) cholesterol, and oxidized LDL (ox-LDL), but decreased eicosatrienoic acid. The rs174537T group showed significantly increased γ-linolenic acid and ox-LDL, and decreased eicosadienoic acid, eicosapentaenoic acid (EPA)/α-linolenic acid (ALA), and IL-6. After 3 years, the rs174537T group had lower AA (P < 0.001), AA/DGLA (P = 0.019), EPA, DPA, EPA/ALA, and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) (P = 0.011) than rs174537GG. Changes in AA (P = 0.001), AA/DGLA (P = 0.017), EPA, DPA, EPA/ALA, and urinary 8-epi-PGF2α (P < 0.001) were significantly different between the groups after adjusting for baseline values. Overall, changes in AA positively correlated with changes in urinary 8-epi-PGF2α (r = 0.249, P = 0.007), plasma ox-LDL (r = 0.199, P = 0.045), and serum IL-6 (r = 0.289, P = 0.004).
  
  
  CONCLUSIONS
  Our data show that FADS polymorphisms can affect age-associated changes in serum phospholipid long-chain PUFAs, Δ5-desaturase activity, and oxidative stress in middle-aged nonobese men. In particular, the rs174537T allele did not show the age-associated increases in AA and Δ5-desaturase activity seen with the rs174537GG genotype.
authors.affiliation: National Research Laboratory for Clinical Nutrigenetics/Nutrigenomics, Yonsei University, Seoul, South Korea.
authors.forename: Seul Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kwak
authors.forename: Jean Kyung
authors.initials: JK
authors.lastname: Paik
authors.forename: Jey Sook
authors.initials: JS
authors.lastname: Chae
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D000886:Anthropometry; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D016009:Chi-Square Distribution; D003404:Creatinine / Q000652:urine; D000090943:Delta-5 Fatty Acid Desaturase; D004032:Diet; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D018384:Oxidative Stress; D010743:Phospholipids / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D008055:Lipids; D010743:Phospholipids; D003404:Creatinine; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human
keywords: FADS gene; age-related changes; nonobese men; oxidative stress markers; serum phospholipid polyunsaturated fatty acids